What is the role of aminoglycosides (e.g. gentamicin, tobramycin) in the treatment of urinary tract infections (UTIs)?

Role of Aminoglycosides in Urinary Tract Infection Treatment

Aminoglycosides are ideal agents for single-dose treatment of uncomplicated lower UTIs but should be reserved for complicated UTIs or when other less nephrotoxic alternatives are unavailable due to their potential toxicity profile. 1

Pharmacological Properties and Efficacy

Aminoglycosides have several properties that make them effective for UTI treatment:

• High urinary concentrations (25-100 times higher than plasma levels) 1
• Prolonged therapeutic levels in urine after a single dose 1
• Excellent activity against most uropathogens, including multidrug-resistant organisms 1, 2
• Microbiological cure rates of 87-100% in lower UTIs 1, 2

Clinical Applications

Recommended Uses:

1. Complicated UTIs:

   • FDA-approved for complicated UTIs caused by susceptible organisms 3, 4
   • Effective against P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., and S. aureus 3, 4

2. Carbapenem-resistant Enterobacterales (CRE) UTIs:

   • Single-dose aminoglycoside receives a weak recommendation for CRE-associated cystitis 1
   • Plazomicin (novel aminoglycoside) is recommended as a treatment option for CRE-UTI 1

3. Single-dose therapy for lower UTIs:

   • Particularly useful when adherence is a concern 2
   • Pooled microbiologic cure rate of 94.5% with sustained cure in 73.4% of patients at 30 days 2

Not Recommended For:

• Uncomplicated initial UTI episodes unless causative organisms are susceptible only to aminoglycosides 3
• First-line empiric therapy when less toxic alternatives are available 1

Dosing Strategies

1. Single-dose regimen:

   • Preferred for uncomplicated lower UTIs 1, 2
   • Provides therapeutic urinary levels for days 1, 5
   • Allows outpatient treatment with fewer injections 5

2. Multiple-dose regimen:

   • For complicated UTIs or pyelonephritis 4
   • Standard dosing: 3 mg/kg/day divided into 3 equal doses 4
   • Life-threatening infections: up to 5 mg/kg/day 4

3. Administration route:

   • Intravenous or intramuscular for systemic infections 3, 4
   • Intravesical administration (80 mg gentamicin) may be effective for recurrent UTIs in patients with intermittent bladder catheterization 6

Safety Considerations

Nephrotoxicity:

• KDIGO guidelines recommend avoiding aminoglycosides unless no suitable, less nephrotoxic alternatives are available 1
• Risk factors: high serum concentrations, prolonged therapy, renal impairment, concurrent nephrotoxic drugs 4
• Nephrotoxicity is typically reversible 7

Ototoxicity:

• Can cause irreversible auditory and vestibular toxicity 4
• Risk factors: high serum concentrations, prolonged therapy, renal impairment, concurrent ototoxic drugs 4
• In utero exposure can result in permanent ototoxicity 7

Monitoring Recommendations:

• For single-dose therapy: minimal monitoring required (0.5% toxicity rate) 2
• For multiple-dose regimens: monitor drug levels when treatment exceeds 24-48 hours 1
• Consider renal function monitoring during treatment 4

Practical Recommendations

1. For uncomplicated lower UTIs:

   • Consider single-dose aminoglycoside when adherence is a concern or resistance to first-line agents is present 2
   • Monitor for signs of toxicity, though risk is minimal with single-dose therapy 2

2. For complicated UTIs:

   • Use aminoglycosides as part of targeted therapy based on culture results 3, 4
   • Consider once-daily dosing in patients with normal renal function 1
   • Monitor drug levels when treatment exceeds 48 hours 1

3. For recurrent UTIs in catheterized patients:

   • Consider intravesical gentamicin (80 mg daily) when infections are caused by multidrug-resistant organisms 6

Pitfalls and Caveats

• Lower efficacy in patients with urinary tract abnormalities 2
• Not recommended for asymptomatic bacteriuria (promotes resistance without clinical benefit) 8
• Avoid in pregnancy if possible due to potential fetal harm 4
• Consider local resistance patterns before empiric use 8

Aminoglycosides remain valuable agents for UTI treatment, particularly in the era of increasing antimicrobial resistance, but their use should be judicious given their potential toxicity profile.